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To experimentally determine the environmental influences acting on P. aeruginosa virulence factor expression in biofilms and understand the catalytic mechanism of one of them (the surface tethered aminopeptidase AaaA)

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Pseudomonas aeruginosa is an important opportunistic pathogen. It is a problem for the immunocompromised and has attained superbug notoriety since it is evident in hospitals and has inherent resistance to antibiotics. P. aeruginosa is a major cause of morbidity in cystic fibrosis sufferers and also causes infections of burns and trauma wounds. This can cause a problem after surgical procedures. Many of the P. aeruginosa virulence factors are secreted or found on the cell surface where they are ideally located to contact host cells. We have recently characterized one of these and found that it is an arginine-specific aminopeptidase (AaaA). We know that this protein is required for full virulence in a mouse chronic wound model, and also for colonisation of reconstructed human skin where it can influence the innate immune response. However, we do not know the target or regulatory control of AaaA. We will use our collection of clinical strains, defined mutants, reporter strains and overproduction strains to understand what factors control AaaA, and how it functions.

The group you will join is funded by the EU and Industry, and is integrating a range of novel technological platforms through active collaborations to uncover the complex regulatory pathways at work and deliver this exciting data. Techniques include novel optical nanosensors (in collaboration with Jonathan Aylott), Mass Spectroscopy (in collaboration with Morgan Alexander) and Raman Sectroscopy (in collaboration with Ioan Notingher).

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University View Website.

References

Luckett, J.C.A, Darch, O., Watters, C., AbuOun, M., Wright, V., Paredes-Osses, E., Ward, J., Goto, H., Heeb, S,, Pommier, S., Rumbaugh, K., Camara, M., and Hardie, K.R. (2012) A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity. Plos Pathogens. 8(8):e1002854.

Ruparell A., Dubern JF., Ortori C., Harrison, F., Halliday N., Emtage A., Ashawesh, M., Laughton C., Diggle, SP., Williams P., Barrett D., and Hardie K.R (2016) The fitness burdens imposed by synthesising quorum sensing systems. Nature Scientific Reports. 6, 33101 http://biorxiv.org/content/early/2016/04/26/050229.

Related Subjects

How good is research at University of Nottingham in Biological Sciences?

FTE Category A staff submitted: 90.86

Research output data provided by the Research Excellence Framework (REF)

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